Randomized, double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of MAP0004 (orally-inhaled DHE) in adult asthmatics

MAP0004 (a proprietary formulation of dihydroergotamine mesylate [DHE]) for inhaled delivery is being developed for acute migraine treatment. Because asthma and migraine often occur as co-morbid conditions, it is considered important to study the safety of MAP0004 in a population of asthmatic adults and to confirm that the pharmacokinetics of DHE, when inhaled by asthmatic subjects, were comparable to a population of healthy volunteers. The safety, tolerability, and pharmacokinetics of orally-inhaled MAP0004 administered by the Tempo inhaler were studied in adult asthmatics.This was a randomized, double-blind, placebo-controlled study of two doses of inhaled MAP0004. Eligible subjects were randomized in a 2 : 1 ratio to MAP0004 or placebo and observed for 4 h after each dose. Pharmacokinetic parameters were determined pre-dose and up to 36 h post-dose.Among 19 subjects, geometric mean AUC(0-36) was 6754 pg.h/mL and geometric mean AUC(0-inf) was 7483 pg.h/mL. Geometric mean t(max) was 9.6 min, geometric mean C(max) was 3174 pg/mL, and geometric mean t((1/2)) was 9.5 h. Overall, 13 of 19 (68%) subjects reported at least one adverse event, most commonly nausea, vomiting, dysgeusia, and headache.MAP0004 results in rapid and efficient systemic absorption in asthmatic subjects. Systemic DHE concentrations were similar to those previously reported in healthy subjects, and no clinically relevant safety issues were observed. While this small study was suitable for pharmacokinetic analysis and conclusions, MAP0004 use in migraineurs with concomitant stable asthma should be supported by larger studies of longer duration to confirm that it does not present additional safety risks compared to non-asthmatic migraineurs.